class: center, middle, inverse, title-slide # Pre and post natal exposure to phthalates<br>VS Eye tracker measurements<br>in SEPAGES ### M. Rolland ### 11/10/2021 --- # Neurodevelopmental disorders -- * Include * intellectual disability * attention-deficit/hyperactivity disorders * learning disabilities * autism spectrum disorders (ASD) -- * In France ~12% of children -- * Recent increase in prevalence -- * Usually diagnosed using neurodev scores * CBCL * SRS * BRIEFP * IQ -- * Known risk factors include * genetic * epigenetic * **environmental** --- # Phtalates -- * Widespread exposure in general population * personal care products (e.g., cosmetics, fragrances, and shampoos), * food packaging * indoor residential environments (e.g., polyvinyl chloride (PVC) flooring and plastics, vinyl tiles, and shower curtains) -- * Several banned in France in children's toys and food packaging -- * Little is known regarding health effect of their substitutes -- * **Exposure to phtalates** among suspected risk factors --- # Eye tracker  --- # Eye tracker  --- class: inverse, center, middle # 1. Study the impact of pre and post natal exposure to phtalates on child neurodevelopment --- class: inverse, center, middle # 2. Explore how eye tracker measurements predict neurodevelopmental scores --- class: inverse, center, middle # METHODS --- # SEPAGES  --- # SEPAGES  --- # SEPAGES  --- # SEPAGES  --- # SEPAGES  --- # SEPAGES  --- # BabyLab tasks  --- # Outcome definition -- * **Attraction to novel faces**: time spent looking at novel faces of *face exploration* task * [New-Old]/[New+Old] * positive = more time spent looking at new face * negative = more time spent looking at old face -- * **Fixation duration**: mean fixation duration of *scene exploration* task and *face exploration* tasks -- * **Reaction time**: mean time to disengage from central target in *target pursuit* task --- # Stats -- 1. Descriptive analysis -- 2. Correlation analysis between EyeTracker (ET) and neurodev scores -- 3. Multivariate model: mixed effects, single chemical, single exposure time -- a. Covariate selection -- * among suspected **confounders** and outcome **predictors**: tobacco, maternal age, child sex, HAD score, maternal education, parity, professional status, breastfeeding duration, maternal IQ, child age, and experiment time -- b. Dose response shape -- c. Final model: `$$outcome_i = exposure_{jk} + covariates + 1|id$$` -- * `\(i\)`: ith outcome (fixation duration/attraction to novel faces/reaction time) * `\(j\)`: jth compound (MEP, MnBP, MiBP, etc) * `\(k\)`: kth exposure time (T2, T3, M12) --- class: inverse, center, middle # RESULTS --- # Phtalate levels  * All phtalates detected in 100% samples --- # EyeTracker measurements  * Strong relationship with age for fixation duration and reaction time --- # Correlation analysis - correlation heatmap  --- # Correlation analysis - PCA  --- # Correlation analysis - PCA  --- # Correlation analysis -- * Non IQ scores positively associated -- * IQ independendant from non IQ scores -- * Attraction to novel faces * Not associated with IQ * Negatively associated with non IQ scores -- * Fixation duration * Positively associated with non IQ scores * Negatively associated with IQ -- * Reaction time * Negatively associated with non IQ scores * Negatively associated with IQ --- # EyeTracker score predictors  -- * Child age strong predictor for all 3 outcomes -- * Shorter reaction times for girls -- * Positive association between maternal age and Fixation Duration and Reaction Time --- # Final multivariate models  -- * Attraction to novel faces * Weaker for tertile 2 and 3 exposure to MEP in the 3rd trimester * Stronger for tertile 2 and 3 exposure to MnBP in the 2nd and 3rd trimester --- # Final multivariate models  * Fixation duration * Longer for tertile 3 exposure to DiNP in the 3rd trimester --- # Final multivariate models  * Reaction time * Shorter for tertile 2 and 3 exposure to DEHP and DiNP in the 3rd trimester * Negatively associated with exposure to MEP in the 12 months on infancy and exposure to MnBP in the 3rd trimester of pregnancy --- class: inverse, center, middle # DISCUSSION --- # Main results -- * Eye tracker scores associated with traditional neurodevelopmental scores -- * Could be an interesting complement to diagnose neurodevelopment issues (can be done at a younger age and potentially less biased) -- * Associations are observed between exposure to phthalates (both pre and post natal) and EyeTracker scores --- class: inverse, center, middle # REMAINING WORK --- # To do -- * Need to validate our outcome interpretation and the meaning of each association direction -- * Explore other scores (gaze location, percent time spent looking at eyes, etc) -- * Explore interactions with sex and age --- class: inverse, center, middle # thank you :) --- class: inverse, center, middle # ANNEXES --- # Attraction to novel faces properties >Reaction to novelty is a keystone in cognitive development. The capacity to attentionaly orient toward new stimuli is linked to the capacity of detecting changes in the environment which implies memory of previous event, faces or other types of stimulations (Pascalis, O., & de Haan, M. 2003). Recognition memory and novelty preference: What model. Progress in infancy research, 3, 95-119. . Positive ratio means attention to novel faces while negative ratio indicate attention to previously seen faces (preference for familiar faces). --- # Fixation duration properties >En millisecondes. La durée de fixation est difficile a interpréter. Elle reflète l'encodage de l'information mais aussi le contrôle saccadique. Si je ne controle pas bien les saccades elles interviennent plus fréquement ce qui entraine une baisse de la durée de fixation. Je dirais que les durées très grandes comme les très courtes peuvent indiquer un fonctionnement atypique. A longer fixation duration indicates difficulty in extracting information, or it means that the object is more engaging in some way (Just & Carpenter, 1976). However, research in 4- to 10-month-olds suggest that mean fixation duration in infancy is positively associated with effortful control (β=.20, R2= .02,p=.04) and negatively with surgency (β=-.37,R2= .07,p=.003) and hyperactivity-inattention (β=-.35,R2= .06,p=.005) in childhood. These findings suggest that individual differences in mean fixation duration in infancy are linked to attentional and behavioral control in childhood. It could be a predictor of ADHD ( Papageorgiou et al., 2014). --- # Reaction time properties >In milliseconds. RT reflect the capacity to disengage from previous location to attend to a stimulus. Here it is an attentional marker of the interest for faces. It is know to decrease in age from 386 ms (SD 70) in 5-month-olds to 333 (59) and 293 ms (42) in 7- and 12-month-olds respectively (Rose et al., 2002).